Analysis of an NGS retinopathy panel detects chromosome 1 uniparental isodisomy in a patient with RPE65-related leber congenital amaurosis

Fabiana Louise Motta, Rafael Filippelli-Silva, Joao Paulo Kitajima, Denise A. Batista, Elizabeth S. Wohler, Nara L. Sobreira, Renan Paulo Martin, Juliana Maria Ferraz Sallum

Research output: Contribution to journalArticlepeer-review


Purpose: This study aims to demonstrate the possibility of detecting segmental uniparental isodisomy (iUPD) using a next-generation sequencing gene panel by reporting a Leber congenital amaurosis (LCA) case caused by a homozygous pathogenic variant in RPE65 (c.1022 T > C:p.Leu341Ser) inherited exclusively from the proband’s mother. Methods: Samples from the trio (proband, mother, and father) were sequenced with a next-generation sequencing (NGS) retinopathy gene panel (224 genes) and the VCF file containing all variants was used in order to determine single nucleotide variant (SNV) counts from each sample across all chromosomes. Results: Trio analysis showed that of 81 Chr1 inherited variants 41 were exclusively maternal, including 21 homozygous. The other 40 variants were common to both parents. On remaining autosomal chromosomes (Chr2-22) 645 inherited variants were found, 147 of them were exclusively maternal and 132 exclusively paternal. Based on these NGS data, it was possible to note that the proband’s chromosomes 1 are more similar to his mother’s chromosome 1 than his father’s, suggesting the pathogenic homozygous variant found in this patient was inherited exclusively from the mother due to uniparental maternal isodisomy. Conclusions: This study presents a secondary analysis pipeline to identify responsible variants for a phenotype and the correct inheritance pattern, which is a critical step to the proper and accurate genetic counseling of all family members. In addition, this approach could be used to determine iUPD in different Mendelian disorders if the sequencing panel identifies variants spread throughout the genome.

Original languageEnglish (US)
Pages (from-to)553-560
Number of pages8
JournalOphthalmic genetics
Issue number5
StatePublished - 2021


  • RPE65 gene
  • Uniparental isodisomy
  • diagnosis
  • gene panel
  • next-generation sequencing

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Ophthalmology
  • Genetics(clinical)


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